This application for continuation of our program project focuses on the modulation of the sympathetic nervous system and the integrative role of the sympathetic nervous system on local blood flow regulation. The program has been expanded from five projects and two cores to eight projects and two cores. Four of the eight projects represent expansion of the program which involves the disciplines of pharmacology, physiology and molecular biology. PROJECT I entitled Neurogenic Hypertension in the Subhuman Primate involves the characterization of interactions between the sympathetic nervous system and mechanisms involved in sodium homeostasis in the sinoaortic denervated baboon. PROJECT II entitled Sympathetic Nervous System and Sodium Dependent Hypertension will investigate central mechanisms responsible for the increased activation of the sympathetic nervous system during sodium retention. The major objective of PROJECT III entitled Area Postrema Modulation of the Arterial Baroreflex is to determine the importance of the area postrema in modulating the arterial baroreflex. The goals of PROJECT IV entitled Metabolic Modulation of Sympathetic Vasoconstriction are to determine how vasodilator metabolites modulate the vascular response to increases in sympathetic outflow. PROJECT V entitled Somatic Afferent Inputs to Nucleus Tractus Solitarius will investigate the integration of somatic afferents in the nucleus tractus solitarius and the potential consequence on the regulation of sympathetic outflow. PROJECT VI entitled Sympathetic Regulation of Skin Blood Flow in Humans will examine the involvement of sympathetic vasoconstrictor and vasodilator mechanisms in the regulation of skin blood flow. PROJECT VII entitled Interactions of SHR-Derived Endothelium and Vascular Smooth Muscle will study the interactions between endothelial and vascular development and function in spontaneously hypertensive rats. PROJECT VIII entitled Mechanisms of Enhanced Tyrosine Hydroxylase Transcription will investigate the molecular genetic mechanisms which are involved in regulating tyrosine hydroxylase. These strongly related projects, which are supported by an Administrative Core A and Biochemical Assay Core B form the structure of this program project. The individual goals of each project will allow us to achieve the overall goal of the program.